分类： 生物学 >> 生物数学 提交时间： 2025-07-14
Xiuzhu Liu
Li Wei
Rong Zhang
Jiaxin Chen
Tongshan Zhang
Junrui Hua
Jufang Wang
Jinpeng He
Xiaodong Xie
摘要： Senescence is a cellular response closely associated with genotoxic stress and plays a critical role in determining cell fate following irradiation exposure. Primary cilia, sensory organelles on the cell surface, detect and transmit diverse signaling cues. However, the relationship between primary cilia and senescence in long-term cell fate decisions after ionizing radiation (IR) remains poorly understood. Here, we show that DNA-dependent protein kinase catalytic subunit (p-DNA-PKcs) co-localized with centromeres during various mitosis stages, while during interphase, p-DNA-PKcs is confined to the nucleus in tumor cells. Following irradiation exposure, primary cilia are formed and persistently maintained at high levels in senescent tumor cells. Inhibition of DNA-PKcs enhances primary cilia formation, while combines inhibition with siDNA-PKcs and irradiation reduces cilia generation, moreover, Chloral hydrate-induced primary cilia removal results in senescent cell death and decreases p-DNA-PKcs protein expression. Notably, treatment with the apoptosis inducer ABT263, also leads to increased cell death and a decreased incidence of primary cilia. Inhibition of either primary cilia or DNA-PKcs further enhances the radiosensitivity of tumor cells. These findings suggest that p-DNA-PKcs contributes to primary cilia formation after irradiation and plays a critical role in both the induction and maintenance of cellular senescence.
分类： 生物学 >> 细胞生物学 提交时间： 2025-01-19
摘要： Mesenchymal stem cells (MSCs) possess the ability to differentiate into various cell types,facilitating the repair of damaged tissues and organs while enhancing their functions, thereby playing a role in healing age-related decline. However, MSCs are also subject to aging, leading to a significant reduction in their self-renewal capacity and differentiation potential. We observed a marked increase in cell size among aged MSCs, with GLS1 expression levels in these enlarged cells being significantly higher compared to those in normal cells. Inducing cellular aging with D-galactose further elevates GLS1 expression and is accompanied by an increase in cell size. Moreover, GLS1 overexpression may enhance the expression of key glycolytic enzymes through the upregulation of FOXK2, leading to metabolic reprogramming. Conversely, overexpressing GLS1 in normal cells does not directly elevate the expression of aging-related markers, nor does it impede cell proliferation. However, GLS1 overexpression appears to diminish differentiation potential by inhibiting the Wnt/β-Catenin signaling pathway. Thus, inhibited differentiation ability of senescent MSCs, which expressed higher GLS1, may be a protective mechanism for the body to prevent the risk on newly generated tissue after the differentiation. This study investigates the relationship between GLS1 and aging, proposing that GLS1 could serve as a potential biomarker for assessing MSC quality, thereby minimizing differences in effects during MSCs-based therapy. Furthermore, elucidating the association between GLS1 and MSC senescence is crucial for advancing our understanding of the intricate mechanisms underlying MSC aging.
分类： 生物学 >> 植物学 >> 植物生理学 提交时间： 2016-05-03
摘要： Leaf senescence is the final leaf developmental process that is regulated by both intracellular factors and environmental conditions. The mitogen-activated protein kinase (MAPK) signaling cascades have been shown to play important roles in regulating leaf senescence; however, the component(s) downstream of the MAPK cascades in regulating leaf senescence are not fully understood. Here we showed that the transcriptions of ZmMEK1, ZmSIMK1, and ZmMPK3 were induced during dark-induced maize leaf senescence. Furthermore, in-gel kinase analysis revealed the 42kDa MAPK was activated. ZmMEK1 interacted with ZmSIMK1 in yeast and maize mesophyll protoplasts and ZmSIMK1 was activated by ZmMEK1 in vitro. Expression of a dominant negative mutant of ZmMEK1 in Arabidopsis transgenic plants induced salicylic acid (SA) accumulation and SA-dependent leaf senescence. ZmMEK1 interacted with Arabidopsis MPK4 in yeast and activated MPK4 in vitro. SA treatment accelerated dark-induced maize leaf senescence. Moreover, blockage of MAPK signaling increased endogenous SA accumulation in maize leaves. These findings suggest that ZmMEK1-ZmSIMK1 cascade and its modulating SA levels play important roles in regulating leaf senescence.
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